Cell Cycle Control and CancerWhat happens when things go wrong?

Essential Question(s)

1. How does the cell regulate the stages of the cell cycle and what happens when regulation fails?

Cell Cycle Review

G2

S G1

Mmetaphase

prophaseanaphase

telophase

interphase (G1, S, G2 phases)mitosis (M)cytokinesis (C)

C

Frequency of Cell Division

MMitosis

G1Gap 1

G0Resting

G2Gap 2

SSynthesis

Turn and Talk 1

Overview of Cell Cycle Controls

ENTERMITOSIS

homologouschromosomes

sister

chromatids

homologous

chromosomes

Turn and Talk 2

How do cells know when to divide?

Internal Cell Cycle Controls

Internal Cell Cycle Controls

Cdk / G1cyclin

MPF

G2

S

G1

CM

G2 checkpoint

APC

ActiveInactive

ActiveInactive

InactiveActive

mitosis

Cytokinesis

MPF = Mitosis Promoting FactorAPC = Anaphase Promoting Complex

• Replication completed• DNA integrity

Chromosomes attached at metaphase plate

M / Spindle checkpoint

• Growth factors• Nutritional state of cell• Size of cell

Restriction Point

Turn and Talk 3

Cancer

What Causes Cancer?

Loss of Cell Cycle Control in Cancer

Multiple Hit Hypothesis

p53 Tumor Suppressor Gene

DNA damage is causedby heat, radiation, or chemicals.

p53 allows cellswith repairedDNA to divide.

Step 1

DNA damage iscaused by heat,radiation, or chemicals.

Step 1 Step 2

Damaged cells continue to divide.If other damage accumulates, thecell can turn cancerous.

Step 3p53 triggers the destruction of cells damaged beyond repair.

ABNORMAL p53

NORMAL p53

abnormalp53 protein

cancercell

Step 3The p53 protein fails to stopcell division and repair DNA.Cell divides without repair todamaged DNA.

Cell division stops, and p53 triggers enzymes to repair damaged region.

Step 2

DNA repair enzymep53protein p53

protein

External Cell Cycle Controls

Tumor Angiogenesis

Tumor Metastasis

Increased Cell Growth in Tumors in vivo

0.00E+00

4.00E+06

8.00E+06

1.20E+07

0 2 4 6 8 10 12

Days After Plating

Cell

Num

ber (

cells

/ml)

pMEXneosJ1dnRBP-J #1dnRBP-J #9

Increased Cell Growth in Tumors in vivo

PECAM1 (CD31)

40X 40X

dnRBP-J #9pMEXneo

Anchorage Independent Growth in vitro

pMEXneo sJ1 dnRBP-J #1 dnRBP-J #9

Tumor Metastasis in vitro

PECAM1 (CD31)

10X 40X

dnRBP-J #9

pMEXneo

Enduring Understandings1. When a cell specializes, it often enters into a stage where it no

longer divides, but it can reenter the cell cycle when given appropriate cues. Non-dividing cells may exit the cell cycle, or hold at a particular stage in the cell cycle.

2. The cell cycle is a complex set of stages that is highly regulated with checkpoints, which determine the ultimate fate of the cell.

3. The cell cycle is directed by internal controls or checkpoints.

4. Cyclins and cyclin-dependent-kinases control the cell cycle.

5. External signals also provide stop-and-go signs at the checkpoints.

6. Cancer results due to disruptions of the cell cycle.